Bordetella pertussis the causative agent of whooping cough secretes or releases during exponential growth, a highly active adenylate cyclase (AC) that has been demonstrated to be a major toxin, as well as an immunoprotective antigen in experimental infection of mice.
This enzyme shares in common with the secreted adenylate cyclase (edema factor) of Bacillus anthracis, the anthrax bacillus, and with the eucaryotic adenylate cyclase, the property of being activable by a eucaryotic protein, calmodulin (CaM). Experiments with enriched preparations of AC have provided some evidence that this enzyme is able to invade various eucaroytoc cells and subsequently, to promote a rapid, non regulated, increase of intracellular cAMP. This cAMP-mediated cytopathic effect is clearly distinguished from the deregulation of eucaryotic adenylate cyclase produced by another toxin of B.pertussis, the pertussis toxin.
It is known since its discovery that B. pertussis undergoes spontaneous phase variations associated with loss of expression of several phenotypical characteristics including AC activity. However it is not clear whether these phenotypical changes result from the lack of expression (synthesis, export and/or release) of the molecule or its loss of catalytic activity.
By using a set of anti-AC antibodies, the inventors have checked the expression of AC antigen in virulent or avirulent B.pertussis variants and corrected this immunological detection with enzymatic activity.
By carrying out their work, they have found in virulent and avirulent crude bacterial extracts, a protein devoid of catalytic adenylate cyclase activity, but having valuable antigenic properties.
It is then an object of the invention to provide a new protein useful as an immunoprotective antigen in human and animals particularly against Bordetella infections and toxic processes by pathogenic bacteria.